This is a proposal to investigate neurotensin and cholecystokinin in the function of the mesolimbic dopamine system using behavioral and neurochemical tests. Studies will focus on the ventral tegmental area (VTA) and the nucleus accumbens (NAC). This project grows out of reports that rats will self-inject morphine and neurotensin in the VTA and will self-inject amphetamine, dopamine and cholecystokinin in the NAC. It appears that animals work for chemical control over the mesolimbic system. In addition, it has been reported that the stimulus properties of i.p. amphetamine generalize to NAC amphetamine, and that dopamine and cholecystokinin can act synergistically to induce locomotion. We propose to study neurotensin and cholecystokinin, mprphine and amphetamine, and dopamine by a dose-response analysis of their reinforcing and stimulus generalization properties. Positive results with these agonists will be followed up with (a) receptor antagonists to determine relevance to synaptic neuropharmacology, (b) 6-hydroxy-dopamine to determine dependence on mesolimbic dopamine release, (c) regional assays to measure dopamine turnover, and (d) local dialysis to measure catecholamine and cholecystokinin release. This proposal will clarify the function of neurotensin and cholecystokinin in modulating the mesolimbic system and their relation to morphine and amphetamine.